Transfusion of Convalescent Plasma for the Early Treatment of Patients With COVID-19 (TSUNAMI)

Transfusion of Convalescent Plasma for the Early Treatment of pneumonIa Due to SARSCoV2: a Multicenter Open Label Randomized Control Trial

No specific therapeutic agents or vaccines for COVID-19 are available. Several therapies, are under investigation, but the antiviral efficacy of these drugs is not yet known. The use of convalescent plasma was recommended as an empirical treatment during outbreaks of Ebola virus in 2014, and a protocol for treatment of Middle East respiratory syndrome coronavirus with convalescent plasma was established in 2015. Accordingly, we hypothesized that use of convalescent plasma transfusion could be beneficial in patients infected with SARS-CoV-2.

This is a multicenter prospective randomized clinical trial to evaluate safety and efficacy of early use of convalescent plasma in patients with SARS-CoV2 pneumonia.

Primary endpoint will be the efficacy, evaluated as the need of invasive mechanical ventilation defined by PaO2/FiO2 ratio <150.

Secondary endpoints will be: mortality rates, time to invasive mechanical ventilation, time to virological cure, length of hospital stay, toxicity.

Patients with SARS-CoV2 pneumonia not requiring mechanical ventilation (both non invasive and invasive) will be randomized 1:1 to receive or not convalescent plasma. Patients in the plasma group will receive 200 ml of convalescent plasma, continuing already administered standard therapy, while patients in the control group will continue to receive the standard therapy. A rescue therapy will be allowed in case of clinical worsening.

Patients will be followed-up until 30 days from randomization.

Study Overview

• Status: Terminated
• Conditions: SARS-CoV 2; COVID
• Intervention / Treatment: Biological: CONVALESCENT PLASMA

Detailed Description

This is a multicenter prospective randomized open-label clinical trials. Patients with pneumonia due to SARS-CoV-2 will be included and randomized to receive or not convalescent plasma.

Convalescent plasma will be collected by cured patients with previous diagnosis of COVID-19. More specifically, inclusion and exclusion criteria for donors will be the following.

Inclusion criteria for donors:

• age > 18 and <60 years
• confirmed diagnosis of COVID-19: PCR on nasopharynx swab or positive IgG
• presence of 2 negative nasopharynx swabs for patients with previous positive swab and presence of 1 negative nasopharynx swab for patients with positive IgG

Exclusion criteria for donors:

• age < 18 ys or >60 ys
• other conditions that controindicate blood donation

Collected plasma will undergo all procedures for blood preparation. Plasma will be tested with enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody titers.

Patients eligible for the study will be selected among hospitalized patients with SARS-CoV2 pneumonia. More specifically, the following criteria will used for inclusion in the study.

Inclusion criteria for recipients:

• age >18 ys
• confirmed diagnosis of SARS-CoV2 pneumonia
• PaO2/FiO2 200-350

Exclusion criteria for recipients:

• PaO2/FiO2 <200
• need of non invasive or invasive mechanical ventilation

Patients will be randomized 1:1 to receive or not convalescent plasma. All patients will be followed-up for 30 days after randomization.

Primary endpoint will be the need of mechanical ventilation, defined as PaO2/FiO2 <150.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Pisa, Italy, 56124
    • Azienda Ospedaliero Universitaria Pisana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Any gender
• Age > 18 years on day of signing informed consent
• Informed written consent for participation in the study
• Virological diagnosis of SARS-CoV-2 infection (real-time PCR)
• Hospitalized due to clinical instrumental diagnosis of pneumonia
• PaO2/FiO2 ratio 200-350

Exclusion Criteria:

• mechanical ventilation (both invasive and non-invasive)
• PaO2/FiO2<200
• known hypersensitivity to immunoglobulin or blood components

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Patients in the intervention group will receive 200 cc of convalescent plasma	Biological: CONVALESCENT PLASMA; Convalescent plasma will be collected by healthy donors, cured by COVID-19 and, after standard preparation and dosage of neutralizing antibodies, will be administered to patients with SARS-CoV2 pneumonia
No Intervention: Control; Patients will continue to receive standard therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need of invasive mechanical ventilation	Need of invasive mechanical ventilation defined as PaO2/FiO2 <150	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rates	Thirty-day mortality rates	30 days
Time to invasive mechanical ventilation	Days from randomization to invasive mechanical ventilation	30 days
Time to virologic cure	Days from randomization to virologic cure defined as 2 consecutive negative nasopharynx swabs	30 days
Length of hospital stay	Days from randomization to discharge or death	30 days
Adverse events	Occurrence of adverse events	30 days

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero, Universitaria Pisana
• Investigators: Principal Investigator: Francesco Menichetti, Azienda Ospedaliero, Universitaria Pisana

Publications and helpful links

General Publications

• Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Apr 28;323(16):1582-1589. doi: 10.1001/jama.2020.4783.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Actual): September 30, 2020
• Study Completion (Actual): September 30, 2020

Study Registration Dates

• First Submitted: May 16, 2020
• First Submitted That Met QC Criteria: May 16, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Actual): November 12, 2020
• Last Update Submitted That Met QC Criteria: November 9, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: pneumonia; covid-19; SARS-CoV2; convalescent plasma
• Other Study ID Numbers: Tsunami

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No